Solid-state conformations of oligopeptides possessing an -(Aib-ΔZPhe)2- segment†

Abstract

An X-ray crystallographic analysis was carried out for Boc-(Aib-∆ Z Phe) 2 -Aib-OMe 1 and Boc--Pro-(Aib-∆ Z Phe) 2 -Aib-OMe 2 (Aib = α-aminoisobutyric acid; ∆ Z Phe = α,β-dehydrophenylalanine; Boc = tert-butoxycarbonyl; OMe = methoxy) to provide detailed conformational data for oligopeptides possessing an -(Aib-∆ Z Phe) 2 -segment. Both peptides adopted a typical 3 10 -helical conformation characterized by <φ> = 52.8Њ, <ψ> = 29.3Њ, and <ω> = Ϫ173.8Њ for the average values of the four residues of the -(Aib-∆ Z Phe) 2 -segment in peptide 1, and <φ> = 54Њ, <ψ> = 27Њ, and <ω> = Ϫ175Њ for those in peptide 2. The preference for a 3 10 -helix in the -(Aib-∆ Z Phe) 2 -segment is ascribed to the presence of Aib and ∆ Z Phe residues being strong inducers for the formation of a 3 10 -helix. In peptide 2, the Nterminal -Pro residue adopted a semiextended conformation, leading to a left-handed screw sense for the following achiral segment. This result was also supported by conformational energy calculation, in which the -Pro residue leading to a left-handed 3 10 -helical segment prefers a semiextended conformation rather than a right-handed helical conformation.

Chiral interaction in Gly‐capped N‐terminal motif of 310‐helix and domino‐type induction in helix sense

“…[24][25][26][27][43][44][45][46][47][48][49][50][51][52][53][54][55] Achiral peptides composed mainly of (D Z Phe-Aib) units, including peptide 2, were found to adopt 3 10 -helix in solution [14][15][16][17][18][19] and in crystal states. 56,57 Theoretical study also supports that the (D Z Phe-Aib)-based periodic sequence has a propensity to take a helical form. [14][15][16][17][18][19]56,58 These backgrounds suggest that peptide 1 prefers 3 10 -helical conformation, which is indeed supported from the following FTIR and NMR studies.…”

“…Therefore, peptide 1 is shown to have high propensity to adopt 3 10 -helical conformation, as exemplified in analogous peptides. [14][15][16][17][18][19][20][56][57][58] …”

Crystal structure of achiral nonapeptide Boc–(Aib–ΔzPhe)4–Aib–OMe at atomic resolution: Evidence for a 310‐helix

“…The segment can be expected to generate two “enantiomeric” (left‐handed and right‐handed) helices, because Aib15–25 and Δ Z Phe26–37 are known as achiral residues for promoting a 3 10 ‐helix. Actually, NMR spectroscopy revealed that achiral peptides possessing an –(Aib–Δ Z Phe) n – segment ( n = 2–4) adopt a 3 10 ‐helical conformation in solution 38–42. Conformational energy calculations also supported a marked helix‐forming tendency in oligopeptides possessing an –(Aib–Δ Z Phe) n – segment 11, 38.…”

Handedness preference and switching of peptide helices. Part II: Helices based on noncodedα‐amino acids

“…Contributions in this area are much less numerous (Refs. ) than those in each separated area (for the only available review article comparing Aib and ΔPhe, see Ref. ).…”

“…The X‐ray diffraction structures of two (strictly sequential) achiral peptides, one pentapeptide and one nonapeptide, containing exclusively Aib and ΔPhe were solved . Not surprisingly, in view of the effective 3 10 ‐helix inducing propensity of their building blocks, each peptide adopts a typical enantiomeric 3 10 ‐helical conformation.…”